Peripheral Vasodilation in Obese Humans
肥胖人群的外周血管舒张
基本信息
- 批准号:8515512
- 负责人:
- 金额:$ 52.34万
- 依托单位:
- 依托单位国家:美国
- 项目类别:
- 财政年份:2011
- 资助国家:美国
- 起止时间:2011-09-01 至 2016-06-30
- 项目状态:已结题
- 来源:
- 关键词:AccountingActivities of Daily LivingAcuteAddressAdultAgeAgingAnimal ModelAntsArteriesBiological AvailabilityBiopsyBlood VesselsBlood flowBody Weight decreasedCardiovascular DiseasesChronicClinicalDataDetectionDevelopmentDiabetes MellitusDiseaseDisease ProgressionDoppler UltrasoundDrug Delivery SystemsElderlyEndothelial CellsEndotheliumEnvironmentEnzymesEpidemicEventExerciseExercise ToleranceExhibitsFunctional disorderGoalsHealthHealth Care CostsHumanHyperglycemiaHypertensionImpairmentInfusion proceduresInsulin ResistanceInterventionLimb structureLinkMeasuresMechanicsMediatingMetabolicMetabolic DiseasesMetabolic syndromeMicrocirculationMolecularMuscleNitric OxideObesityObesity associated diseaseObstructive Sleep ApneaOxidantsPathway interactionsPatientsPeripheralPeripheral ResistancePharmaceutical PreparationsPhenotypePhysical activityPhysiologicalPhysiologyPlayProcessProphylactic treatmentProstaglandinsProtocols documentationPublic HealthQuality of lifeRattusReactive Oxygen SpeciesRecoveryRegulationResearchRestRiskRoleSamplingSignal TransductionSkeletal MuscleStagingTestingTimeVasoconstrictor AgentsVasodilationVasodilator Agentsage effectbasecardiovascular risk factorcombatconstrictiondesigndiet and exercisedisease diagnosisemerging adultglucose uptakeimprovedimproved functioningnovelnovel therapeuticspre-clinicalprematureprogramsrelating to nervous systemresponserestorationtherapeutic targetvasoconstrictionyoung adult
项目摘要
DESCRIPTION (provided by applicant):
The overall goal of this research program is to investigate the obesity-related changes in microvascular function that initiate the cardiovascular disease process. The growing population of obese adults is predicted to create a large public health burden in the next few decades. Skeletal muscle accounts for the majority of peripheral resistance and glucose uptake in humans. Decreased muscle vasodilation likely contributes to hypertension and sets the stage for hyperglycemia-both hallmarks of metabolic syndrome and diabetes. Thus, low muscle blood flow in obese humans may contribute to reduced exercise capacity-this in turn sets the stage for development of long-term cardiovascular diseases like diabetes. We propose to study younger obese "metabolically health" adults (18-35 yrs), without confounding effects of age, metabolic syndrome, or diabetes- before the negative effects of obesity can exert their full negative impact. The general hypothesis is that obesity impairs endothelium dependent dilation (EDD) and exercise vasodilation via increased reactive oxygen species (ROS) and reductions in vasodilator signals and increased vasoconstrictor signals. Our preliminary data suggest young obese adults exhibit reduced EDD and exercise vasodilation, and acute ROS scavenging improves both. We will test our hypotheses by arterial drug infusion to test EDD mechanisms in lean and obese humans. We will use similar approaches to test vascular mechanisms controlling blood flow during dynamic exercise. Next, we will test EDD and exercise vascular responses before and after a diet and exercise intervention, where we can parcel out whether physical activity or weight loss plays a larger role in vascular improvements. Finally, we will sample artery endothelial cells from these same subjects to identify molecular pathways that change with obesity as potential therapeutic targets. These studies integrate physiologic, pharmacologic, and molecular approaches to test our hypotheses. We have several exciting preliminary findings that support our hypotheses, and have designed a complementary set of Aims the will soundly address our research questions. A multi-disciplinary, state-of-the-art approach will be used to pursue these aims, which will provide fundamental mechanistic understanding of EDD and exercise mechanisms responsible for reduced blood flow in obese humans. Our novel findings will guide the development of novel therapeutic strategies for obesity and other diseases, including obstructive sleep apnea, metabolic syndrome and diabetes.
描述(由申请人提供):
项目成果
期刊论文数量(0)
专著数量(0)
科研奖励数量(0)
会议论文数量(0)
专利数量(0)
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WILLIAM G SCHRAGE其他文献
WILLIAM G SCHRAGE的其他文献
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{{ truncateString('WILLIAM G SCHRAGE', 18)}}的其他基金
Human cerebral blood flow regulation: sex, mechanism, and stress differences
人类脑血流调节:性别、机制和应激差异
- 批准号:
10650368 - 财政年份:2020
- 资助金额:
$ 52.34万 - 项目类别:
Human cerebral blood flow regulation: sex, mechanism, and stress differences
人类脑血流调节:性别、机制和应激差异
- 批准号:
10407466 - 财政年份:2020
- 资助金额:
$ 52.34万 - 项目类别:
Insulin resistance, cognitive health, and perfusion of the adolescent brain
胰岛素抵抗、认知健康和青少年大脑灌注
- 批准号:
9980475 - 财政年份:2019
- 资助金额:
$ 52.34万 - 项目类别:
Aging and Microvascular Dysfunction in Human Skeletal Muscle
人体骨骼肌的衰老和微血管功能障碍
- 批准号:
7587863 - 财政年份:2009
- 资助金额:
$ 52.34万 - 项目类别:
Aging and Microvascular Dysfunction in Human Skeletal Muscle
人体骨骼肌的衰老和微血管功能障碍
- 批准号:
7770776 - 财政年份:2009
- 资助金额:
$ 52.34万 - 项目类别:
Muscle Pump and Chemical Dilation in Exercise Hyperemia
运动充血中的肌肉泵和化学扩张
- 批准号:
6710162 - 财政年份:2002
- 资助金额:
$ 52.34万 - 项目类别:
Muscle Pump and Chemical Dilation in Exercise Hyperemia
运动充血中的肌肉泵和化学扩张
- 批准号:
6447034 - 财政年份:2002
- 资助金额:
$ 52.34万 - 项目类别:
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